1. Field of the Invention
Present invention relates to a sensing method for biopolymers and a sensing device therefor.
2. Description of the Related Art
In the investigation of biotechnology, it becomes frequently necessary to prepare a large amount of a particular antigen, although the preparation of the antigen generally requires a great deal of labor, time and expenses. However, a marked reduction in time and expenses required for the purification of the antigen becomes possible with the use of the monoclonal antibody which specifically binds with the antigen. For example, if we inject an antigen into an animal such as mouse, a corresponding antibody is formed in the body whereas the antibody forming cell dies out. Accordingly, an immortalized antibody forming cell (hybridoma), which has been prepared by cell fusion techniques, is conventionally used in the purification of the said antigen. However, there are various kinds of hybridomas, and it is necessary to select the hybridoma which specifically recognizes the target antigen to form monoclonal antibody.
In the selection process, a plurality of small containers (wells) in which the antigen is pre-adhered are prepared, the solutions of monoclonal antibody produced by hybridoma are pipetted into them, and then the quantity of reacted monoclonal antibody is examined in each well. Conventionally, the determination of the quantity is carried out by means of fluorescent or radioactive labeling. In the said conventional fluorescent labeling method, however, the accuracy of the estimation is lowered due to the fluorescent fading, so called bleaching phenomenon, thus the estimation should be carried out in a short time. The use of radioactive labeling is also undesirable from the viewpoint of safety measure, since the use of radioactive ray is limited in a specified controlled area and the risk for radiation exposure of operator should be considered.
As for the sensing devices for antigen antibody reaction, the present inventors have proposed devices detecting the magnetic signals with high sensitivity by means of a superconducting quantum interference device (SQUID) magnetic sensor, in which AC magnetic field is imposed on the antibody labeled with magnetic fine particles with several microns in diameter in the course of the antigen antibody reaction (for example, see patent documents 1 and 2). In addition, a method to impose DC magnetic field has been also proposed (for example, see patent documents 3 and 4). Although these methods have partly solved above described drawbacks, the sensitivity of the detection is not sufficient yet.
[Patent document 1] Japanese unexamined patent application publication no. 2001-133458
[Patent document 2] Japanese unexamined patent application publication no. 2004-061144
[Patent document 3] Japanese unexamined patent application publication no. 11-068180
[Patent document 4] Japanese unexamined patent application publication no. 2004-157072
In light of the foregoing, it is an object of the present invention to provide a highly sensitive sensing method for biopolymers and a sensing device therefor, by amplifying the magnetic signal generated from the biopolymer reaction using the thermo-responsive magnetic nano particles.